Cognitive Control Function and Moderate-to-Severe Traumatic Brain Injury: Functional and Structural Brain Correlates
Abstract
Clinical signs of traumatic brain injury (TBI) such as altered- or complete loss of consciousness,
other neurological signs, and findings based on conventional neuroimaging,
represents important information for initial treatment and further follow-up of TBI survivors.
However, not all real-life problems after TBI are easily detected by conventional
imaging methods or neurological exams. This is particularly evident when trying to assess
the more subtle effects of TBI, such as cognitive and emotional problems, that are often
experienced in the chronic stage, after the initial recovery period has passed. The main aim
for this thesis was to extend current knowledge on functional and structural changes in the
brain after moderate-to-severe TBI by means of advanced neuroimaging methods, and to
relate these findings to injury-related variables and functional measures known to be important
for outcome. A particular focus was on investigating cognitive control function, as
this has been demonstrated to play an especially important role for functional outcome
after TBI. In order to reach this aim, several studies with different but related perspectives
were performed, and four papers (Paper I – IV) based on these studies are included in this
thesis.
In Paper I, a large group of healthy participants was included in a study in order to validate
a clinically relevant task protocol that could measure both adaptive and stable cognitive
control processes in the brain by means of blood-oxygen-level-dependent (BOLD)
functional magnetic resonance imaging (fMRI). Results from this study gave further
support for a core network of cognitive control, with overlapping activations for both
stable and adaptive processes, comprised by brain regions bilaterally in the insula (and
adjacent cortices) and dorsal medial frontal cortex. It was also established that in this
particular task, adaptive cognitive control processes by and large were distributed in more
anterior regions of the prefrontal cortex as compared to stable cognitive control processes.
Another novel and important finding, was that only stable cognitive control processes
were affected by time on task (TOT), indicating that this contrast might be particularly
sensitive for detecting adaptive changes in the brain. In Paper II, it was demonstrated that executive, emotional and behavioral problems were
more frequently reported in chronic moderate-to-severe TBI survivors as compared to
healthy controls. The results also indicated that identification of traumatic axonal injury
(TAI) and symptoms of depression in an earlier phase after injury, might give a warning of
later problems. Furthermore, self-report measures of cognitive control seemed to extend
the information obtained from performance-based measures.
In Paper III, it was shown that neuronal correlates of adaptive and stable cognitive control
processes were differently affected by moderate-to severe TBI. Moreover, TBI survivors
exhibited increased TOT related BOLD activation related to stable cognitive control
processes in the right inferior parietal lobe and right prefrontal cortex. Increases in BOLD
activations had a dose-dependent relationship with injury severity, with increased activation
with more severe injury. Interestingly, increased BOLD activations after TBI were
related to better self-reported cognitive control function in everyday-life situations, indicating
a compensatory role for these activations.
In paper IV, it was shown that more severe injury based on clinical signs, and findings on
conventional MRI evaluations, was related to more pronounced alterations of white matter
microstructure in a wide range of tracts as measured with diffusion tensor imaging
(DTI). Reduced white matter integrity in TBI survivors was also associated with worse
global outcome, and poorer cognitive control function as measured by performance-based
measures. No association was found between any of the DTI measures and self-reported
cognitive control function.
The findings presented in this thesis demonstrated that a broad assessment is warranted in
order to optimize our understanding and follow-up of TBI patients. Also, it was shown
that subtle changes in brain structure and function, not necessarily detectable with conventional
imaging tools, might still have an important impact on how TBI survivors are
able to cope with every-day life. A particularly interesting finding with possible clinical
implications was that performance-based cognitive control function in chronic TBI was
related to subtle structural changes in the brain as measured with DTI, whereas selfreported
problems were exclusively related to functional adaptations as measured with fMRI. In general, knowing that self-reported cognitive control function in chronic moderate-
to-severe TBI survivors is associated with functional changes in the brain, gives an
important perspective when seeing patients where such problems are not easily explained
by conventional neuropsychological measures. More than that, as these functional changes
were shown to play a potential compensatory role, this might indicate a potential target
for neuro-rehabilitation.
Has parts
Paper 1: Olsen, A., Brunner, J.F., Evensen, K.A.I., Garzon, B., Landro, N. I., Haberg, A.K. The functional topography and temporal dynamics of overlapping and distinct brain activations for adaptive task control and stable task-set maintenance during performance of an fMRI-adapted clinical continuous performance test. Journal of Cognitive Neuroscience 2013; 25, 903-919 © 2015 The MIT Press http://dx.doi.org/10.1162/jocn_a_00358Paper 2: Finnanger, T., Olsen, A., Skandsen, T., Lydersen, S., Vik, A., Evensen, K.A.I., Haberg, A. K., Andersson, S., Indredavik, M. Self-reported executive, emotional and behavioural function 2-5 years after moderate-to-severe traumatic brain injury – a prospective followup study. Submitted manuscript. Is not included due to copyright.
Paper 3: Olsen, A., Brunner, J. F., Evensen, K. A. I., Finnanger, T., Vik, A., Skandsen, T., Landro, N. I., Haberg, A. K. Altered cognitive control activations after moderate-to-severe traumatic brain injury and their relationship to injury severity and everyday-life function. Cerebral Cortex 2014. http://dx.doi.org/10.1093/cercor/bhu023 © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals. permissions@oup.com
Paper 4: Håberg, A. K., Olsen, A., Moen, K. G., Schirmer-Mikalsen, K., Visser, E., Finnanger, T., Evensen, K. A. I., Vik., A., Skandsen, T., Eikenes, L. White matter microstructure in moderate-to-severe traumatic brain injury: the impact of acute phase injury related variables and associations with global outcome, performance-based and self-reported cognitive control function. Article first published online: 30 DEC 2014, ©2014 Wiley Periodicals, Inc. http://dx.doi.org/10.1002/jnr.23534